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Introduction: Hyperoxia and hypocapnia have been associated with poor outcome after cardiac arrest (CA). However, definitions of hyperoxia and hypocapnia were based on a limited number of blood gas analyses per patient. Also, no data are available on the combined effects of altered arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) on outcome. Methods: We reviewed all comatose patients admitted after successful resuscitation from CA to a single academic medical center between January 2007 and April 2013. Inclusion criteria were as follows: age ≥18, non-traumatic arrest; and survival ≥24 hours after admission. We analyzed all arterial blood gas data for the first 24 hours after hospital admission. We a priori defined hypocapnia and hypercapnia as at least one PaCO2 ≤30 mmHg and ≥50 mmHg, respectively; we a priori defined hypoxemia and hyperoxemia as at least one PaO2 ≤60 mmHg and ≥300 mmHg, respectively. A CPC score of 3-5 at 3-months was used to define poor neurological outcome. Results: Of 207 patients, 78 (37%) had hypocapnia only, 46 (22%) had hypercapnia only, 42 (20%) had hypocapnia and hypercapnia and 41 (20%) had neither; 78 (23%) patients had hypoxemia only, 44 (21%) had hyperoxemia only, 7 (3%) had hypoxemia and hyperoxemia and 109 (53%) had neither (p<0.001). The median number of blood gas analyses was 10 [8-12] per patient. Among the patients, 139 (67%) had a poor neurological outcome. Patients with hypocapnia and hypercapnia had similar rates of poor neurological outcome (73% and 59%) than those without or with both PaCO2 abnormalities (69% and 64%, p=0.42). Patients with hypoxemia and hyperoxemia also had similar rates of poor neurological outcome (70% and 70%) than those without or with both PaO2 abnormalities (72% and 85%, p=0.85). In patients with hypocapnia and hypercapnia mortality was higher if concomitant hypoxemia or hyperoxemia were present (6/8 and 6/6, respectively) compared to patients without PaO2 abnormalities (12/24; p=0.05). Conclusions: In this retrospective study, PaCO2 abnormalities were more frequent than PaO2 alterations after CA. PaO2 and PaCO2 abnormalities were not associated with poor outcome. Hypoxemia and hyperoxemia increased the risk for poor outcome only among those patients concomitantly exposed to large variations in PaCO2.